GVAX Pancreas Vaccine (With CY) and CRS-207 With or Without Nivolumab

A Randomized Phase 2 Study of the Safety, Efficacy, and Immune Response of GVAX Pancreas Vaccine (With Cyclophosphamide) and CRS-207 With or Without Nivolumab in Patients With Previously Treated Metastatic Pancreatic Adenocarcinoma

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02243371

Enrollment

Registered

2014-09-17

Start date

2015-01-02

Completion date

2017-07-21

Last updated

2021-04-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Previously Treated Metastatic Adenocarcinoma of the Pancreas

Brief summary

The primary objective of this study is to compare the overall survival (OS) of subjects with previously treated metastatic pancreatic cancer treated with cyclophosphamide (CY)/nivolumab/GVAX pancreas vaccine followed by nivolumab/CRS-207 (Arm A) to subjects treated with CY/GVAX pancreas vaccine followed by CRS-207 (Arm B).

Interventions

BIOLOGICALCRS-207

1 × 10\^9 CFU administered IV on Day 2 of Cycles 3-6

DRUGnivolumab

3 mg/kg administered IV on Day 1 of Cycles 1-6

BIOLOGICALGVAX

5x10\^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2

DRUGCY

200 mg/m\^2 administered IV on Day 1 of Cycles 1 and 2

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Age ≥18 years. * Have histologically- or cytologically-proven adenocarcinoma of the pancreas. Patients with mixed histology will be excluded. * Have metastatic disease. * Have failed only 1 prior chemotherapy regimen for metastatic pancreatic cancer. * Patients with the presence of at least one measurable lesion. * Patients acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator). * ECOG performance status 0 or 1. * Life expectancy of greater than 3 months. * Patients must have adequate organ and marrow function defined by study-specified laboratory tests. * Must use acceptable form of birth control while on study. * Ability to understand and willingness to sign a written informed consent document.

Exclusion criteria

* known history or evidence of brain metastases. * Had surgery within the last 28 days * Have received any non-oncology vaccine therapy used for prevention of infectious diseases including seasonal vaccinations within 28 days of study treatment. * Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, GVAX or CRS-207 * Systemic steroids within the last 14 days * Use more than 3 g/day of acetaminophen. * Patients on immunosuppressive agents. * Patients receiving growth factors within the last 14 days * Known allergy to both penicillin and sulfa. * Severe hypersensitivity reaction to any monoclonal antibody. * Have artificial joints or implants that cannot be easily removed * Have any evidence of hepatic cirrhosis or clinical or radiographic ascites. * Have significant and/or malignant pleural effusion * Infection with HIV or hepatitis B or C at screening * Significant heart disease * Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures * Unable to avoid intimate contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen. * Are pregnant or breastfeeding. * Have rapidly progressing disease

Design outcomes

Primary

Measure	Time frame	Description
Overall Survival (OS)	2 years and 7 months	OS will be measured from date of randomization until death or end of followup (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis).

Secondary

Measure	Time frame	Description
Progression-free Survival (PFS) in Metastatic Pancreatic Cancer Patients	2 years and 7 months	PFS is defined as the number of months from the date of randomization to disease progression (progressive disease \[PD\] or relapse from complete response \[CR\] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.
Immune-related Progression-free Survival (irPFS) by IRRC in Metastatic Pancreatic Cancer Patients	2 years and 7 months	irPFS is defined as the number of months from the date of randomization to disease progression (PD or relapse from CR as assessed using irRC RECIST 1.1 criteria) or death due to any cause. Per irRC criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in tumor burden compared with baseline, Progressive Disease (PD) is \>20% increase in tumor burden compared with nadir, Stable Disease (SD) is \<30% decrease in tumor burden compared with baseline or \<20% increase in tumor burden compared to nadir.
Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity	2 years and 7 months	When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.
Number of Participants With Partial Response (PR) or Complete Response (CR) as Defined by RECIST 1.1 in Metastatic Pancreatic Cancer Patients	2 years and 7 months	Per RECIST 1.1 criteria, PR is defined as =\>30% decrease in sum of diameters of target lesions and CR is the disappearance of all target lesions.
Tumor Marker Kinetics (CA 19-9) in Patients With Baseline Abnormal Levels as Measured by Number of Participants With Stable or Responding CA19-9 Concentration	120 days	Number of participants with stable or responding (\<50% increase of serum CA19-9 concentration) at 120 days.
Time to Progression (TTP) by RECIST 1.1 in Metastatic Pancreatic Cancer Patients	2 years and 7 months	Time to progression (TTP) is defined as the time from randomization to the date of documented disease progression as defined by RECIST 1.1 criteria. Individuals are censored at the date of the last radiological assessment that occurs prior to any of the following: death, switch to another anti-cancer therapy, or end of follow-up. Individuals without follow-up or baseline measurements are censored at 1 day. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.

Countries

United States

Participant flow

Participants by arm

Arm	Count
CY/ GVAX/ CRS-207/ Nivolumab CRS-207: 1 × 10\^9 CFU administered IV on Day 2 of Cycles 3-6 GVAX: 5x10\^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6 CY: 200 mg/m\^2 administered IV on Day 1 of Cycles 1 and 2	51
CY/ GVAX/ CRS-207 CRS-207: 1 × 10\^9 CFU administered IV Day 1 of Cycles 3-6 GVAX: 5x10\^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 CY: 200 mg/m\^2 administered IV on Day 1 of Cycles 1 and 2	42
Total	93

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event (unrelated)	0	1
Overall Study	Death (unrelated)	2	4
Overall Study	Lack of Clinical Benefit	0	1
Overall Study	Progressive Disease (clinic & radio)	35	24
Overall Study	Withdrawal by Subject	0	2

Baseline characteristics

Characteristic	CY/ GVAX/ CRS-207	Total	CY/ GVAX/ CRS-207/ Nivolumab
Age, Continuous	63.2 years STANDARD_DEVIATION 9.28	63.4 years STANDARD_DEVIATION 8.6	63.6 years STANDARD_DEVIATION 8.08
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	2 Participants	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants	84 Participants	46 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants	7 Participants	3 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	5 Participants	10 Participants	5 Participants
Race (NIH/OMB) Black or African American	4 Participants	4 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	33 Participants	77 Participants	44 Participants
Sex: Female, Male Female	18 Participants	32 Participants	14 Participants
Sex: Female, Male Male	24 Participants	61 Participants	37 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	45 / 51	36 / 42
other Total, other adverse events	46 / 51	40 / 42
serious Total, serious adverse events	5 / 51	1 / 42

Outcome results

Primary

Overall Survival (OS)

OS will be measured from date of randomization until death or end of followup (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis).